PROJECT SUMMARY/ABSTRACT The Cancer Cell Biology (CCB) Program of Winship Cancer Institute of Emory University is a laboratory-based translational program focused on understanding the changes in function of human cells as a result of cell transformation. Deregulation of the intra- and extra-cellular functional interactions of the cell's proteome leads to abnormal cell phenotypes, and these processes are at the root of the cancer process. The research within the CCB Program is organized into three scientific themes: (1) Cell Survival and Death Mechanisms, which focuses on intrinsic and extrinsic regulation of cell death through understanding and targeting both the Bcl-2 family and of death receptors; (2) Tumor?Stroma Interactions, which seeks to understand how tumor cells communicate and adhere, the biology of cancer stem cells, angiogenesis and immune interactions, and the process of EMT that is important for cell motility, invasion, and metastasis; and (3) Cancer Cell Metabolism, which focuses on how genetic alterations affecting signaling pathways impact the posttranslational modifications of key metabolic enzymes and redirect metabolic intermediates toward the synthesis of biomolecules of cell growth and proliferation. Under the leadership of Erwin Van Meir, PhD (leader) and Lawrence Boise, PhD (co-leader) the CCB Program has 36 core members from 16 different departments in the School of Medicine or Emory College. Between 2012 and the present, this highly collaborative group of researchers published 541 cancer- relevant scientific articles. Of these, 94 (17%) were intra- and 163 (30%) were inter-programmatic collaborations, and 214 (40%) involved a collaboration with another cancer center or academic organization. As of March 31, 2016, CCB held $17.7 million in annual total cancer-relevant research funding, of which $12.2 million (69%) was awarded directly from the NCI. The scientific advances driven by the CCB Program are highly significant in that they unravel novel mechanisms underlying cancer formation and growth and, in this process, unveil potential therapeutic targets.